Culture,context,and ethics in the therapeutic use of hallucinogens: Psychedelics as active super-placebos?

Introduction

After decades of prohibition and widespread concern about their mind-altering properties, there has been increasing public, scholarly, and clinical interest in the alleged therapeutic potential of psychedelic substances. Once confined to local indigenous practices predominantly but not exclusively bound to the pre-colonial Americas, the ritualized and institutionalized use of hallucinogens has undergone an important transnational diffusion in the last century. As indigenous practices were transformed to accommodate growing interest from the outside world, ritual hallucinogenic use gradually integrated Western idioms of psychotherapy, personal development, and novel forms of New Age syncretic spirituality. In the Global North, popular assumptions and discourse about psychedelics have also undergone a series of dramatic shifts since the 1960s. After initial hopes of freedom and flourishing stemming from the “free love” movement of the 1960s, psychedelics in the late Cold War era became increasingly associated with CIA experiments, fears of “mind-control,” and a prohibitive public health discourse that emphasized the risks of adverse mental health consequences (Hartogsohn, 2022). Much of the scientific debate on psychedelics at the time focused on the extent to which these substances emulated or actually caused psychosis (Friesen, 2022).

As moral panics about psychedelics have gradually given way to a psychedelic revival (Pollan, 2018), psychedelic drugs are increasingly hailed as a therapeutic panacea thought to enhance creativity and productivity and cure such ailments as depression, anxiety, trauma, and substance use disorder, among others (see Carhart-Harris & Goodwin, 2017, for a review). Despite consensus on the positive outcomes of this pharmacological revolution, some scholars have begun raising cautions about the uncritical acceptance, desirability, medicalization, and commercialization of substances that remain poorly understood (Dupuis, 2021)—and so particularly as they become increasingly divorced from their “traditional” ritual and spiritual contexts. Indeed, the historically novel, culturally specific modalities of self-enhancement, the medical ontologies in which they are framed, and the neurocentric idioms of distress targeted in clinical psychedelic use have remained largely unexamined in the new science of psychedelics.

To address this gap, we invited articles that explored the cultural contexts, assumptions, and ethical implications of this new engagement with psychedelics. Through a variety of lenses and case studies, all the articles in this special issue emphasize the importance of context—ecological, historical, social, narrative, ritual—required to understand, operationalize, and mobilize psychedelic therapies in all their relevant dimensions. A powerful critique to emerge from all contributors is thus that current medical and neuroscientific approaches, with their near-exclusive emphasis on brain chemistry, fail to address a myriad of contextual factors without which ethical and effective (as opposed to efficacious) therapeutic modalities cannot be mobilized.

The psychedelic renaissance and the question of epistemic justice

We are currently witnessing what has been called a “psychedelic renaissance” (Pollan, 2018). The biomedical appropriation of substances once embedded in rich traditional, cultural, ritual, and spiritual contexts, as pointed out by Schenberg and Gerber (2022a) for the study of ayahuasca, may result in epistemic injustice for Indigenous communities that pioneered their use but have their knowledge and experience ignored or discounted. Schenberg and Gerber (2022a, 2022b) have sought to address these injustices—which in their view also entail epistemological errors, as a correct understanding of psychedelic therapies cannot divorce them from cultural context—by studying the effects of psychedelic substances in their local context, with the collaboration of local experts. As another potential compromise, some scholars have argued for the therapeutic mobilization of traditional psychedelic practices in the context of their respective medical systems, on the grounds of their demonstrated efficacy in randomized controlled trials (Ona et al., 2022). How to ethically implement such medical pluralism (or whether, where, and when medical pluralism is desirable) remains a thorny question. Labate et al. (2022), for example, in their response to Schenberg and Gerber, ask whether the “validation” of Indigenous practices with the tools and epistemologies of Western science can perpetuate the subordination of non-Western ways of knowing. They raise further questions about competing claims to intellectual property in the case of ayahuasca, whose use has also been central to syncretic religious movements that have been historically marginalized in Brazil (see also Smith et al. (2022), for further discussion of the issue of intellectual property).

Psychedelics and context: Placebo effects, set and setting

Another concern to emerge from the detailed attention to the importance of contextual factors in the psychedelic experience in the contributions to this special issue is about the limitations of a reductionist approach to therapy endorsed by the biomedical appropriation of psychedelics. A foreseeable future, where serotonergic psychedelics (psilocybin, DMT, ayahuasca) would be marketed as cleaner, “greener” psychiatric medications, would leave little room for a nuanced understanding of the social and existential contexts in which distress arises on the one hand, and the relevant factors and dimensions of the therapeutic encounter in which psychedelic substances may act as a healing enhancer on the other.

According to one now-popular story, serotonergic psychedelics drastically reduce habitual constraints on perception (increase brain entropy, in the language of computational neuroscience) by increasing the functional connectivity of disparate brain networks that do not habitually communicate with another (Gobbi et al., 2022). Such “unconstraining” of cognitive resources is thus thought to enable one to overcome maladaptive schemas and other symptoms of adverse mental health at unprecedented speed (Carhart-Harris & Friston, 2019; for a critical discussion, see Lifshitz et al., 2018).

In contrast to neuro-reductionist approaches, several contributors to this special issue raise questions about potential placebo, non-specific, or extra-pharmacological effects of psychedelic therapies. Hartogsohn (2022), for example, presents a history of psychedelic use in which he proposes the notion of sociocultural microclimates to describe the distinct types of expectations, intentions, and cultural contexts that have produced drastically different psychedelic experiences in different times and settings. Wong and Raz (2022; see also Kaypak & Raz, 2022), in their review of the current craze for micro-dosing, find no evidence of efficacy beyond placebo and expectancy effects for the wide array of self-improvement indices reported by an ever-growing number of enthusiasts of the practice.

Psychedelic substances have long been known to have effects that are strongly influenced by context. While Timothy Leary (1961) coined the terms “set” and “setting” for these extra-pharmacological factors shaping the drug experience, Claude Lévi-Strauss proposed considering hallucinogens as amplifiers of latent cultural representations (Lévi-Strauss, 1970, p. 13). While cultural variation in psychedelic experience is clear, comparative anthropological data (Dobkin de Rios, 1984; Furst, 1976) suggest that some features of the experiences induced by these substances are similar across cultures (e.g., entoptic phenomena—i.e., mental visual imagery composed of geometric patterns), while others vary extensively cross-culturally (e.g., subjective feeling tone, meaning, or content of the experience). Even if many ethnographers observing homogeneity in the features of the psychedelic experience within the same culture have defended a culturalist approach to these phenomena (Brown, 1978; Dobkin de Rios, 1972; Langdon, 1979; Lévi-Strauss, 1970; Mooney, 1896; Reichel-Dolmatoff, 1972; Wallace, 1959), the paths by which psychedelic experience is shaped by social factors have so far received little scientific attention and require further study.

Using ethnographic data collected at a “shamanic” treatment center in the Peruvian Amazon, Dupuis (2022a, 2022b) aimed to shed light on the underpinnings of these dynamics, which he has termed the “socialization of hallucinations.” Proposing such candidate factors as the education of attention, the categorization of perceptions, and the shaping of emotions and expectations, he argues that cultural background and social interactions organize not only the relationship to the hallucinogenic experience, but also its phenomenological content. In this perspective, psychedelics appear to be powerful catalysts of social affiliation, enculturation, and belief transmission.

While set and setting have long been recognized as important modulators of psychedelic experiences (Gukasyan & Nayak, 2022; Hartogsohn, 2022; Leary et al., 1963), the role of placebo effects has gained increased attention in clinical studies. In a recent experiment designed and supervised by one of us (SV), 33 undergraduate participants consumed a placebo pill that we described as a drug resembling psilocybin (Olson et al., 2020). To boost expectations, confederates subtly acted out the stated effects of the drug and participants were led to believe that there was no placebo control group. To make the study appear more scientific, all researchers wore white lab coats, held identical clipboards and pens, and frequently measured participants’ vital signs. Participants later completed the 5-Dimensional Altered States of Consciousness Rating Scale, which measures changes in conscious experience (Studerus et al., 2010a). The majority (61%) verbally reported some effect of the drug. Several stated that they saw the paintings on the walls “move” or “reshape” themselves, others felt “heavy… as if gravity [had] a stronger hold”; one described a “come down” after being “hit” by another “wave.”

While the importance of context, expectations, suggestion, and other mechanisms of influence on psychedelic experience is amply demonstrated, we caution against dismissing psychedelic therapies as “merely” placebos. This dismissive view ignores the complex processes that underlie placebo responses and the potential significant interactions between these placebo mechanisms and the pharmacological effects of psychedelics. A closer consideration of placebo effects leads us to a more precise claim: psychedelic therapies can be conceptualized as active super-placebos.

Psychedelics as active super-placebos: Context enhancement as a mechanism of action

Psychedelic experiences appear to have a bidirectional relationship to extra-pharmacological factors: they are partially mediated by suggestive influences but are also known to enhance suggestibility. Suggestibility, usually operationalized as an increased tendency to accept and act on the ideas or attitudes of others (Sjoberg & Hollister, 1965), has long been known to be mobilized by psychedelic substances. LSD, mescaline, and psilocybin (Carhart-Harris et al., 2015; Sjoberg & Hollister, 1965), ketamine (Cheong et al., 2011), and cannabis (Kelly et al., 1978), for example, were found to increase suggestibility in healthy subjects. We use the term suggestion in its broad sense as a process of decreased effortful control and increased susceptibility to contextual factors—rather than a discrete psychological trait (e.g., hypnotic suggestibility)—including but not limited to framing effects, verbal and non-verbal suggestions, peer influences, etc.

We suggest then that psychedelic drugs are both responsive to and enhancers of placebo effects. Rather than being inert pills or intervention producing no “real” effects, a more accurate conceptualization of placebos views them as the process of imparting somatic effects (including healing responses) via any other factor than the intended or postulated mechanism of action of a given intervention. Kaptchuk and Miller offer the following operationalization of placebo effects:

In a broad sense, placebo effects are improvements in patients’ symptoms that are attributable to their participation in the therapeutic encounter, with its rituals, symbols, and interactions. (…) This diverse collection of signs and behaviors includes identifiable health care paraphernalia and settings, emotional and cognitive engagement with clinicians, empathic and intimate witnessing, and the laying on of hands. (Kaptchuk & Miller, 2015, p. 8, emphasis added)

On this context-sensitive view of psychedelic drugs, one might posit a dynamic of feedback loops between interactional settings (i.e., rituals) and drugs; that is, of therapeutic encounters that are at once framing of and exponentiated by psychedelic experiences. In placebo studies, “active” components refer to the pharmacological effects of a drug (e.g., arousal induced by caffeine; Edward et al., 2005). Active substances also have placebo effects, that is non-pharmacological responses to sensory cues, expectations, and associative meaning. Moreover, the active effects of a substance can be enhanced through suggestion, or leveraged to increase the impact of further suggestions as patients may interpret signs of active effects as proof that the intervention “works.” In the case of psychedelics, we suggest that the active component greatly enhances receptivity to contextual cues. Thus, while we might define a placebo intervention as one that mobilizes a range of contextual cues to leverage placebo effects (e.g., anticipation, charisma and warm tone of the healer, peer influences, ritual elaboration; see Olson et al., 2021), an active super-placebo—such as a psychedelic healing session—involves a substance that actually enhances the suggestive effects of contextual cues.

A careful consideration of the dynamics of therapeutic encounters, including ritual healing and drug administration, is thus required to better elucidate the workings of psychedelics. Gukasyan and Nayak (2022) summarize four major contextual “common factors” shared by various healing traditions: 1) the therapeutic relationship; 2) the healing setting; 3) the rationale, conceptual scheme, or myth; and 4) the ritual enactment. They discuss the intrinsic role of these factors in psychedelic therapies, and speculate on their contribution to therapeutic effects.

In a recent contribution based on an ethnography of the Takiwasi ayahuasca addiction treatment center in Peru, Dupuis (2021) operationalizes the ritual and “mythical” (or narrative) dimensions of psychedelic encounters. Dupuis presents a detailed analysis of the individual and group trajectories of Western patients who come to adopt a syncretic (Catholic-Indigenous) religious understanding of their substance use issues as “demonic infestations” that can be cured through ritual encounters with plant spirits after ingesting ayahuasca and participating in group debriefing sessions led by a charismatic leader. Observing that individuals with different life histories raised in mostly secular Western contexts came to experience similar visions and adopt similar spiritual worldviews, Dupuis shows how the social setting provides a “narrative reframing” and articulation of experience that is both meaning-enhancing and meaning-crystallizing. This process, ultimately leading to “identity reconfiguration,” seems to play a driving role in the therapeutic effectiveness of these practices.

These observations underline the importance of the different modalities of ritual that have long been theorized by anthropologists to structure and propagate shared meanings and representations. The approach developed by Harvey Whitehouse (2002) distinguishes two types of ritual. Rituals that are rarely performed, physiologically taxing, and arousal-inducing rites of initiation—which Whitehouse terms imagistic modalities—tend to foster a strong sense of solidarity and identity among small groups of participants while retaining heterodox individual meanings (Veissière & Gibbs-Bravo, 2016). In contrast, frequently performed, doctrinal rituals draw on frequently repeated actions and utterances to engage semantic memory and build shared repertoires of meaning. Both of these ritual modalities are key mechanisms of enculturation: for example, highly arousing, “intense” rites of entry or initiation mark changes in identity, which are subsequently rehearsed and engrained through repetition of low-arousal actions like daily prayers and mantra practices.

Outside of formal ritual and healing contexts, one also can identify imagistic and doctrinal elements in the contemporary rites of hospital-based, clinical psychedelic therapy sessions—and even in informal individual or group psychedelic sessions, where the shared meanings of imagistic “tripping” experiences are often negotiated through readings and discussions in online forums.

Ethical implications of the active super-placebo paradigm

The ability of psychedelics to increase a sense of meaning and amplify the causal impact of specific cultural contexts and contents (etiological theories, worldviews, religious beliefs, etc.) appears to be an important mechanism of their therapeutic efficacity. In their afterword to this special issue, Gobbi et al. (2022) thus call for further studies on the mediating impact of cultural meaning and practices on the therapeutic effects of psychedelics.

If the therapeutic efficacy of psychedelics relies (at least in part) on narrative reframing and increased suggestibility induced by these substances, this raises ethical concerns about the kind of influence therapists, shamans, and other facilitators are having over their clients, even when therapy goes well. Comparing three case studies illustrating issues of validation and mediation in therapeutic, neo-shamanic, and research contexts involving psychedelic use, Timmermann et al. (2022) suggest that these meaning-enhancing features of the psychedelic experiences may act as a “double-edged sword.” While they may drive therapeutic benefits, the ability of psychedelics to increase suggestibility along with compelling feelings of reverence and revelation might also lead to problematic consequences. If psychedelics can accelerate the dynamics of belief transmission and profoundly transform participants’ worldviews and behaviors, caution is warranted about the potentially harmful effects of these drugs in certain social contexts.

The issues raised by the articles in this special issue prompt us to call for a middle-of-the-road, compromise view of the therapeutic potential of psychedelic drugs. Psychedelics will neither rid the world of mental illness, nor cause epidemics of psychosis. While the importance of the ritual encounter has been identified as key to ethical and effective therapies, we wish to draw attention also to mechanisms of narrative reframing identified by Dupuis (2022a, 2022b) as potentially crucial to the integration of psychedelic experiences. Rather than exclusively focus on the alleged “freeing up” and “unconstraining” of cognition and schemas involved in psychedelic experiences, we urge scholars and practitioners of psychotic therapies to more closely examine the interpersonal, ideological, and suggestion factors that facilitate the crystallization of new meanings, explanatory models, beliefs, worldviews, values, and behaviors prior to, during, and after psychedelic experiences.

In a sharp challenge to the popular view that associates psychedelic drugs with tolerance, flexibility, and liberal worldviews, Pace and Devenot (2021) examined historical and contemporary case studies of individuals and political movements, from neo-Nazis to cult leaders, who endorsed authoritarian and discriminatory worldviews in spite of, or as a result of, psychedelic use. The second author has encountered similar cases working as part of a clinical team specializing in psychosocial interventions with individuals at risk of violent radicalization. Several patients have described having experiences that contributed to their antisemitic, white nationalist, and millenarian-apocalyptic worldviews while taking psychedelics during periods in which they were already dealing with feelings of rejection, withdrawing from social life, and participating in online forums dedicated to similar themes.

Psychotherapy researchers have long recognized that therapists need to be mindful of patients’ assumptive worlds—that is, the totality of a person's assumptions about what is real in the world (ontology) and how the world ought to be (ethics) (Cantril, 1950; Frank & Frank, 1993). In Jerome Frank's formulation, assumptive worlds involve the automatic formulation of “theories” nested in systems (schemata, scripts, models) of expectations (Frank & Frank, 1993). While Frank argued that therapeutic efficacy needed to be grounded in a shared assumptive world between patients and therapists, he noted that the therapeutic encounter possessed the unique power to indoctrinate the patient into the therapist's assumptive world. We suggest that psychedelic therapies significantly accentuate this risk.

Given their context-enhancing properties, psychedelic substances used in elaborate ritual settings do appear to possess the ability to reshape users’ assumptive worlds with concrete and profound alterations of their disposition toward and dispositions toward specific expectations, affects, and actions. Our compromise view can help clarify how, as potent enhancers of therapeutic mechanisms and encounters in all their cosmological and behavioral dimensions, psychedelics are also potential enhancers of therapeutic harm and malpractice.

Conclusion: Toward “psychedelic know-how”

The articles in this issue of Transcultural Psychiatry make it clear that expectations, cultural meaning, social contexts, and ritual enactments are key contributors of the therapeutic efficacy of psychedelics. Ritual and technical practices, shared symbolic and mythological elaboration, charismatic healers, expectation, anticipation, repetition, trust, relaxation of vigilance, hope, social legitimation and validation (the reassuring sense of witnessing others with shared experiences and results), a feeling of special attention, insight, catharsis, reframing, and a rewarding sense of having earned one's cure through enduring a challenging experience are universal mechanisms of healing that may contribute to every effective intervention. Our itemization of the mechanisms of suggestion and influence leveraged and enhanced by psychedelic therapies, however, should not be interpreted as a dismissal of their distinct value. In addition to their unique pharmacological effects, the capacity of psychedelics to enhance sensitivity to context gives them a special efficacy.

The revival of the therapeutic use of psychedelics in Euro-American societies poses specific challenges. The prohibition of psychedelics in these societies since the 1960s has led to a lack of consensus on ethical guidelines for the use of psychedelics. Even if some attempts to develop informal guidelines and standardize psychedelic use are observed in Western forms of underground psychedelic therapy and integration circles, there is currently no set of authoritative ethical, public health, or professional standards regulating their use. What criteria should determine the ethical use of psychedelics in Western societies in the future? What standard practices can support the remarkable properties of psychedelics? What epistemic authority can these standards rely on for their formulation and application?

While we cannot predict the range of contexts or the precise content of the assumptive worlds that will be leveraged in future psychedelic therapies, we invite scholars, clinicians, and policy makers to pay close attention to the sources of epistemic authority and integrity of the healers, facilitators, and stories that are deployed to assist vulnerable individuals in situations of extreme suggestibility. It is essential to address the ethical issues raised by the use of psychedelics. Neglecting these issues will open the door to reactionary political responses that do not take into account the beneficial potential of these practices. The lack of clear ethical guidelines in Euro-American societies for the use of psychedelics—in contrast to Indigenous societies, in which these uses are frequently framed by traditional norms—seems to partly explain why although research on therapeutic use psychedelics has undergone a revival, informal use has been recently banned in some countries. In France, for instance, the recent prohibition of ayahuasca was motivated by governmental concerns about the possible use of the psychedelic brew by so-called “cult” groups for the purpose of psychological manipulation and “brainwashing” (Dupuis, 2021). While the validity of these concerns is debatable, the apparent ability of psychedelics to increase the acceptance of dubious truth claims and the influence of charismatic leaders has serious ethical implications that need to be carefully considered.

Timmermann et al. (2022) propose a pragmatic framework to address these challenges through an ethical approach that considers the embeddedness of psychedelic experiences in larger historical and cultural contexts, their intersubjective character, and the use of practices which they conceptualize as forms of “psychedelic apprenticeship.” This process of apprenticeship is already apparent in many Indigenous and mestizo shamanic traditions that embody this skillful know-how in social practices such as collective rituals and initiatory practices. Singing, scents, music, interventions, and support during ceremonies are for instance expressions of such know-how. These practices are a crucial source of inspiration to answer the challenging issues raised by the growth of the interest or the therapeutic use of psychedelic substances in the Global North. However, the mobilization of indigenous and mestizo shamanic technical knowledge to improve the therapeutic uses of psychedelics emerging in the Global North also raises ethical questions about cultural appropriation and the fairness of the transmission of this knowledge. Gobbi et al. (2022) express similar concerns and emphasize the importance of developing clinical guidelines and appropriate training for psychedelic-assisted therapies. Close attention to the utilization of cultural and contextual factors will be key in this process.

In the effort to eliminate confounds through tightly controlled randomized controlled trials, biomedical science has too often privileged reductionistic explanatory models that have been translated into impoverished interventions stripped of their “super-placebo” power—that is, of artful utilization of the embodied effects of interactions, symbols, ritual, and spiritual encounters. This “efficacy paradox” has been identified as a central issue in evidence-based medicine (EBM), leading some bioethicists to argue that EBM has much to learn from the so-called alternative and complementary medical interventions that artfully leverage the efficacy of placebo effects (Friesen, 2019). Psychedelic therapies have roots in a diverse range of cultural and spiritual traditions with rich histories in the elaboration of these extra-pharmacological factors.

Thinking through the efficacy of psychedelics in ways that go beyond their pharmacology will yield insights crucial for their safe and effective use in health care settings. We are hopeful that one dividend of this effort will be increased recognition of the importance of ritual and narrative meaning-making and social influence in the effectiveness of all forms of clinical intervention.